Three obesity-related cancers (breast, prostate, colorectal) account for over 1/3 of cancer diagnoses annually and caused 112,520 deaths in 2009. Despite notable progress in early detection and treatment in recent years, African Americans living in the Deep South experience greater cancer burden. Obesity-related cancer death rates for African Americans in Alabama (AL) exceed national and state rates for their white counterparts, as well as national rates among African Americans. Overweight and obesity, which characterizes 76% of African Americans in the US, are implicated in multiple cancers. While reducing excess weight is beneficial in both cancer prevention and survivorship, achieving and maintaining weight loss is complicated by individual, socio-contextual and environmental factors. In the general population, African Americans are often less successful with weight loss than their white counterparts. Cited barriers include lack of social support and environmental challenges (e.g., limited availability of healthy affordable food and access to safe and convenient opportunities for physical activity). Multilevel (individual, interpersonal, environment/policy) approaches have shown promise in achieving and sustaining weight loss; however, to our knowledge, there are no published studies of multilevel weight-loss interventions for African American cancer survivors. The proposed three-group cluster design will enroll 450 overweight African Americans (225 cancer survivors and their 225 family members) residing in 9 rural communities in AL. Communities will be randomly assigned to receive either an evidence-based and culturally-adapted weight loss intervention (Group 1), an evidence-based and culturally-adapted weight loss intervention plus community strategies to support weight loss (Group 2), or no intervention (Group 3). The study seeks to answer the research question: Do evidence-based community strategies supporting weight loss in addition to an evidence-based weight loss program result in greater weight loss among overweight cancer survivors (and their family members) residing in rural communities in the Deep South? Unique elements of the study include its community-based participatory research (CBPR) approach; focus on social and environmental barriers to weight loss success, use of community health advisors to deliver program content, and long-term involvement of targeted counties in a successful academic-community partnership seeking to eliminate cancer disparities. PUBLIC HEALTH RELEVANCE: African Americans living in the rural Deep South experience a greater burden of obesity-related cancers than their white counterparts or African Americans living in other geographic regions. This study will evaluate multilevel weight loss interventions for African American cancer survivors living in the rural Deep South. Findings from this study may decrease risk for cancer recurrence and cancer-related mortality, improve quality of life, and perhaps ultimately increase survival rates for this vulnerable population.